Beyond Traditional Disintegration Testing

We have developed a new technique to better understand what happens to the microstructure inside a tablet during rapid disintegration.

Limitations of Disintegration Testing

In traditional disintegration testing it is difficult to establish any detailed insights into the mechanism of tablet disintegration as the test is merely designed to indicate the time it takes for a tablet or capsule to disintegrate completely, and this is defined as the state "in which any residue of the unit [...] is a soft mass having no palpably firm core". Based on the results of the disintegration test it is judged whether or not the dosage form meets the specification required by the respective pharmacopoeia e.g. for immediate release formulations. Apart from establishing the conformity with such official guidelines the disintegration test yields little additional information and is not very useful to guide rational formulation design.

New insights for immediate release formulations and new opportunities for PAT measurement techniques

Fast and Non-destructive Imaging of Disintegration

Yassin et al. have introduced an alternative method based on terahertz pulsed imaging (TPI) to advance the understanding of how excipients, the dosage form microstructure and the testing conditions affect the disintegration behaviour in immediate release formulations [1]. The method allows for the first time to quantify the disintegration process on time-scales of seconds by measuring the ingress of the dissolution medium into a tablet with high precision and accuracy. Using this data the authors demonstrate that the disintegration process can be explained using theoretical models much like what is known for controlled release dosage forms. It is possible to investigate in detail how subtle changes in disintegrant concentration or the temperature of the dissolution medium affect the disintegration behaviour.

Figure 1: Disintegration process measured using TPI. The method can resolve both the swelling of the tablet as well as the ingress of the dissolution medium into the tablet.

Subtle Differences in Formulation have Profound Effects

A change in crosscarmellose sodium concentration from 2 to 5 wt% has a dramatic effect on the disintegration kinetics, particularly at a water temperature of 20°C. Here the disintegration time of the tablet is one order of magnitude faster at the higher concentration of superdisintegrant.

The study also highlights the enormous effect of the temperature of the dissolution medium on how rapidly a tablet disintegrates: by changing the temperature from 37°C to 20°C the disintegration time reduced from 25 to 5 seconds in a tablet containing 5% croscarmellose sodium (see Figure 2 below).

Figure 2: Disintegration characteristics of tablets made from MCC and superdisintegrant at different concentrations and water temperature (modified from [1]).

The new method is universally applicable to a wide range of formulations for dosage forms with disintegration times from seconds to hours.

PAT Measurements of Porosity – Non-destructive and Meaningful

In addition the paper highlights that measuring the tablet porosity instead of its hardness is potentially a much better PAT method compared to the time consuming and destructive weight/thickness/hardness testing.

It was previously demonstrated that terahertz spectroscopy is an excellent and very promising tool to non-destructively determine the bulk porosity of a tablet in a simple transmission or reflection experiment [2]. Yassin et al. show that such porosity measurements are very sensitive in resolving the disintegration performance of an actual tablet. Given that the terahertz measurements can be performed on millisecond timescales this technology could be developed into a powerful at-line/on-line or even in-line PAT technique.

Figure 3 (left): THz refractive index can be used as a PAT tool to measure the tablet bulk porosity (modified from [2]).